The objective of this research is to examine the factors that influence particle retention in lungs, with particular emphasis on comparing retention patterns in normal animal lungs to retention patterns in well-defined models of lung disease. We seek to describe how disease changes lung architecture and how this in turn affects ventilation and the deposition and clearance of particles. The research plan includes development and characterization of animal models for fibrosis, emphysema, and chronic bronchitis. The distribution of aerosol deposition within the lung will be examined in these disease states, and the location and quantity of deposited particles will be correlated with the location and severity of disease. We will investigate to what extent the altered distribution of retention in diseased lungs might be due to altered breathing pattern. The regional clearance of deposited particles will be described both for normal animals and those with induced pulmonary disease. The information gained from these studies should provide insight into how disease affects the regional deposition and clearance of both environmental and therapeutic aerosols. In order to make rational predictions about the development of further disease, it is important to understand how and where particles are retained within the respiratory tract.